Human genome editing research: what is acceptable?

Following news earlier this year that researchers in China have performed human genome editing for the first time, UK scientists are now seeking permission to genetically modify human embryos. What should the policy on human germline genetic modification be?

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In April this year a research group from Sun Yat-sen University in Guangzhou (China) announced that they had edited the genomes of human embryos for the first time, confirming the widespread rumors that this research was being carried out and launching a debate on the ethical implications.

Controversy

Previously the technique had been used to modify genes in animal zygotes and human cells, but not human embryos. Some scientists believe that human genome editing would be a valuable healthcare tool, as it could theoretically be used to eradicate genetic disease during embryonic development, resulting in the birth of healthy offspring. However, others argue that the use of such a technology would be unethical as firstly genetic changes to embryos are heritable and could therefore result in unexpected effects on future generations and secondly because the technique could be used for unsafe or unethical purposes.

The Sun Yat-sen University researchers utilized tripronuclear zygotes – nonviable embryos obtained from local fertility clinics, which cannot result in a live birth – to investigate CRISPR/Cas9-mediated editing of the HBB gene in human cells. HBB is the gene responsible for β-thalassaemia, a potentially fatal blood disorder, and the team concluded that the technique holds “tremendous promise for both basic research and clinical applications,” but that it is not yet ready for clinical application and therefore that there is further work required to improve the fidelity and specificity of the CRISPR/Cas9 platform.

CRISPR/Cas9 is a technique that allows, compared with previous methods, highly specific gene targeting and editing and therefore the removal of selected genes by via binding and splicing DNA at specific locations. “I believe this is the first report of CRISPR/Cas9 applied to human pre-implantation embryos and as such the study is a landmark, as well as a cautionary tale,” commented George Daley, stem cell biologist at Harvard Medical School (MA, USA). As the results demonstrated issues such as low efficiency of homologous recombination and a number of ‘off-target’ mutations, he continued that the study “should be a stern warning to any practitioner who thinks the technology is ready for testing to eradicate disease genes.”

Ongoing debate

Edward Lanphier, president of Sangamo Biosciences in Richmond (CA, USA), which applies gene-editing techniques to adult human cells, fears that more scientists will now start to work towards improving on the Sun Yat-sen University paper: “The ubiquitous access to and simplicity of creating CRISPRs … creates opportunities for scientists in any part of the world to do any kind of experiments they want.”

In March, the International Society for Stem Cell Research (ISSCR) had called for a moratorium on attempts to apply nuclear genome editing of the human germ line in clinical practice, as they believe that, at present, scientists lack sufficient understanding of the safety and potential long-term risks of germline genome modification. Moreover, the ISSCR asserted that a deeper and more rigorous deliberation was needed on the ethical, legal and societal implications of any attempts at modifying the human germline, if its clinical practice is ever to be sanctioned. After the groundbreaking but controversial research was published in April, the ISSCR called for another moratorium.

More recently, this month the international stem cell policy and ethics expert group the Hinxton Group released a policy statement on heritable human genetic modification in response to the research, stating that any research involving editing the human genome, including research with human embryos, is vital to gain basic understanding of biology and germ cells, and should therefore be permitted. “While there is controversy and deep moral disagreement about human germline genetic modification, what is needed is not to stop all discussion, debate and research, but rather to engage with the public, policymakers and the broader scientific community, and to weigh together the potential benefits and harms of human genome editing for research and human health,” stated Debra Mathews, the Assistant Director for Science Programs at the Johns Hopkins Berman Institute of Bioethics (MD, USA).

Key opinion leaders in the field such as Nobel Laureate David Baltimore (California Institute of Technology, CA, USA) have published papers showcasing their recommendations, the internet is of course brimming with debate and even more group policy debates are still being planned, such as the US National Academy of Sciences’s December meeting to discuss heritable human genetic modification.

Dr Francis Collins, director of the NIH, stated in April that the US government would not fund research for modifying embryo DNA, arguing there were “serious and unquantifiable safety issues”, significant ethical questions and no compelling medical reason to carry out the research. However, in the UK, although gene editing of embryos in IVF treatment is illegal, it is permissible for research purposes (where the embryos are destroyed), under a license.

Latest development

Scientists from the Francis Crick Institute in London in the UK have now applied the Human Fertilisation & Embryology Authority (HFEA) to use CRISPR/Cas9 in embryos to research infertility – the first in the UK to do so. Sarah Chan of the University of Edinburgh (UK) stated the news should be cause for confidence rather than concern: “we should be reassured to know that this work is being carried out under a robust regulatory scheme that ensures high scientific and ethical standards.”

I eagerly await the decision of the UK HFEA, as the outcome will send a clear message about the UK’s take on this contentious subject, as well as the outcomes of further discussions and meetings.

What is your take – should governments be permitting human genome-editing technologies such as CRISPR/Cas9 and human germline genetic modification? If so, what applications should it be permitted to be used for, and how should it be regulated to ensure safe and ethical use? Finally, how best as a community should we discuss the harms and benefits in order to come to a thoroughly considered conclusion?